中药单体CU联合5-FU对胃癌MKN45细胞生长抑制作用

Effect of CU/5-FU on proliferation of gastric cancer cell line MKN45

目的研究姜黄素(CU)和5-氟尿嘧啶(5-FU)单独与联合对人胃癌MKN45细胞生长抑制的效果差异,为临床上联合运用CU和5-FU治疗胃癌提供理论和实验依据。方法用MTT检测不同浓度CU(3.125,6.25,12.5,25,50μmol/L)和不同浓度的5-FU(6.25,12.5,25,50,100μmol/L)单独或联合作用于体外培养的人胃癌MKN45细胞48 h、72h而产生的增殖抑制效应,并对实验数据进行方差分析和析因分析。结果 CU与5-FU单用及联用时,均对体外培养的胃癌MKN45细胞有显著的抑制作用(P<0.05),并且呈时间和剂量依赖效应。两药联合作用48 h,当CU浓度大于2.05μmol/L而5-FU浓度大于4.09μmol/L时,两药表现为协同抑制作用,反之则为拮抗作用;当联合作用72 h,CU浓度大于2.86μmol/L而5-FU浓度大于5.71μmol/L时,两药表现为协同作用,反之则为拮抗作用。结论 CU与5-FU高剂量联合运用对胃癌细胞MKN45的抑制呈现协同效应,低剂量联合呈现拮抗作用。因此,本研究为临床上联合运用CU和5-FU治疗胃癌提供了初步的实验依据。

Objective The growth inhibitory effects of curcumin and 5-fluorouracil（ 5-FU） against human gastric cancer MKN45 cells were investigated in combination or alone to provide theoretical and experimental basis for the treatment of gastric cancer in clinic. Methods MTT assay was used to analyze inhibitory effect on MKN45 cells with different concentrations of curcumin（ 3. 125,6. 25,12. 5,25 and 50 μmol/L） and 5-FU（ 6. 25,12. 5,25,50 and 100 μmol/L） alone or in combination for48 h and 72 h,respectively. And data was analyzed by variance analysis and factorial analysis. Results Curcumin and 5-FU alone or in combination showed a significant dose-and time-dependence on the inhibition of gastric cancer MKN45 cells（ P 〈0. 05） in vitro. Besides,the combination of curcumin and 5-FU emerged a synergetic effect when the concentration of curcumin and 5-FU for 48 h was more than 2. 05 μmol/L and 4. 09 μmol/L,respectively and for 72 h,the concentration of curcumin and 5-FU was more than 2. 86 μmol·L-1 and 5. 71 μmol/L,respectively. However,it exerted antagonistic effect with curcumin（ 〈2. 05 μmol/L） and 5-FU（ 〈4. 09 μmol/L） for 48 h,and curcumin（ 2. 86 μmol/L） and 5-FU（ 5. 71μmol/L） for 72 h. Conclusion Curcumin and 5-FU against gastric cancer MKN45 cells showed synergetic inhibitory effect in high dose but exerted antagonistic effect in low dose. The study provided a preliminary experimental basis for the clinical application of curcumin and 5-FU to treat gastric cancer.